Vascular Communications

TTTS. Vascular Communications

Dating back to Schatz, several observers have considered the vascular anastomoses of monochorionic placentas to be an important factor in the development of TTTS. Most authorities today agree that, to some extent, TTTS arises from unbalanced exchange of blood between twins through these vascular anastomoses. 

Indeed, several studies have shown that ablation of the vascular anastomoses ‘cures’ TTTS.17,18 However, if virtually all monochorionic placentas have vascular communications, why does TTTS develop in only a minority of monochorionic pregnancies? Is there a vascular arrangement that preferentially results in TTTS or is associated with a worsened outcome? 

Regarding the corollary, is there a type of vascular communication that protects against TTTS? These are a few of many questions regarding the pathophysiology of TTTS that remain hotly debated. Only with further basic science and clinical research will we be able to fully answer these questions. The developmental embryology regarding vascular anastomoses in the monochorionic twin placenta is currently not fully known. Placental pathological studies suggest that the vascular arrangement develops in the early embryonic period of development.19 The vessels from the yolk sac develop into the formed chorionic sac at about day 13 following fertilization. The primitive vascular precursors sprout along the inner surface of the primitive chorionic membrane. These vascular precursors begin to fill with blood when the fetal heart begins to pump. 

Whether the vessels become arteries or veins may be determined by directionality and pressure of blood flow. Some of the anastomoses may be kept open, and others atrophy. What influences, if any, dictate the number and type of anastomoses is unknown. One theory involves the unequal split of cells between the divided embryos.20 This may result in differential timing of the fetal heartbeat, forcing the blood through the developing vascular channels. The unequal division of cell mass may not only affect vascular angioarchitecture but also placental mass allocation. Further clarification of the embryology of monochorionic twins as it pertains to the vascular communications will no doubt help in the understanding of the etiology of TTTS. Although previously underestimated, it is now believed that virtually all monochorionic placentas have vascular anastomoses. 

The frequency of vascular anastomoses in twin gestations was well described in a report17 that used comprehensive injection studies to evaluate the vascular anatomy of 278 twin placentas. After exclusion of 97 placentas that were noted to have completely separate placental masses and 19 placentas that were damaged, 162 fused placentas were successfully injected and studied. Ninety-six (59%) were assigned as dichorionic– diamniotic. Of the 56 monochorionic twin placentas studied, vascular communications were identified in 55 cases (98%). 

The single monochorionic placenta in which a vascular communication could not be found had an infarcted region in the area of the vascular equator; this area may have once contained an anastomosis in utero. Four cases, or 7% of the cases with a documented monochorionic placenta, were reported to be complicated by TTTS. In the normal placenta, the chorionic surface vascular anatomy consists of branching vessels from the umbilical cord insertion site. The fetal arteries usually (but not always) course over veins, particularly those of large caliber (Figure 5.2). 

The fetal artery treks along the fetal surface of the placenta to the periphery, where it then dives into its designated cotyledon. The primary branches of the fetal vessels further subdivide into secondary and tertiary stems, from which the terminal villi arise. Thus, each primary villous stem arises into a separate cotyledon. The corresponding vein emerges from the same cotyledon within a few millimeters and courses back to the umbilical cord. Although the fetal artery and vein enter and depart the placental mass in close proximity to one another, the course of these vessels along the surface of the placenta may or may not be related to one another. Each cotyledon usually has only one artery and one vein. Three-vessel (or higher-order) cotyledons may be seen, particularly if one of the vessels serves as a vascular communication between monochorionic twins. The vascular equator divides the monochorionic placenta into two regions. 

This landmark is important not only because it is the region through which the anastomotic vessels traverse but also because it too helps define the relative placental parenchymal volume for each twin (Figures 5.2, 5.5, and 5.6). The placental vascular anatomy may be delineated visually. This is the basis for the fetoscopically guided technique of selective laser photocoagulation of communicating vessels for the treatment of monochorionic twins complicated by TTTS21 (Figure 5.7). As suggested above, it is the vascular equator, not the site of the dividing membrane insertion, which must be identified to allow for the separation of the two vascular circulations during fetal laser surgery. After delivery, injection studies using colored dye, milk, water, or air may further assist in identifying the vascular anatomy19,22 as shown in Figure 5.7c. The umbilical cord may be trimmed to allow unobstructed access to the vessels, or the distal aspect of the cord may be clamped and individual vessels accessed via a fine needle to inject the media. 

The vascular patterns identified after delivery may not necessarily represent the anatomy that was present in utero. Spontaneous alterations of placental anatomy may occur from thrombosis of a vascular communication or infarction of a placental region that may have contained an anastomosis. These placental events may explain the reported cases of both the spontaneous resolution of TTTS as well as the sudden, acute development of TTTS in previously documented ‘normal’ monochorionic pregnancies.23 If a placental event developed remote from delivery, that placental region may be uninterpretable. It is important to note that post-delivery evaluation of placental communications cannot be performed accurately if a remote in utero demise of one twin occurred, or if the placenta was placed in a preservative such as formalin. 

There are two types of vascular communications in a monochorionic placenta. The first type, artery-to-vein (AV) communications, are referred to as deep anastomoses, so-called because the communication takes place at the level of the fetal capillaries in the shared placental cotyledon. This is shown in Figure 5.8. AV anastomoses are unidirectional shunts. Directionality is always from high pressure artery to low pressure vein. Although the anastomoses are ‘deep’, at the level of terminal villi, identification of the origin of the primary arteries and veins on the surface of the chorionic plate allows for identification of all AV communications. 

In the case of TTTS, if the arterial component of the AV communication belongs to the donor, and the venous component to the recipient, the shunt would carry blood from the donor to the recipient fetus. We classify this type of AV anastomosis as an AV-DR, meaning from donor to recipient. In contrast, if the artery belongs to the recipient fetus and the vein to the donor, the direction of the shunt would be from recipient to donor, and is referred to as an AV-RD. Therefore, as long as the artery and vein can be identified, directionality may be assigned. 

Assignment of type of AV anastomoses may be performed both fetoscopically and by gross examination. The second type of placental communication is referred to as a superficial anastomosis, socalled because the vessel directly links both fetal circulations without intervening villous tissue. Superficial anastomoses may be identified fetoscopically by noting the vessels running along the entire surface of the placenta in an often tortuous fashion from one umbilical cord to the other without interruption. 

There are two types of superficial anastomoses: the more common artery-to-artery (AA) anastomosis and the veinto- vein (VV) anastomosis (Figure 5.8). Unlike an AV communication, the superficial anastomoses may be unidirectional or bidirectional, depending on several factors. One factor may be the vascular relationships of the superficial anastomosis to surrounding AV anastomoses. For example, an AA anastomosis with a branching vessel that enters a donor cotyledon may serve as a ‘functional’ DR or RD, depending on where the arterial collision front, which we term the hemodynamic equator, resides within the AA vessel.22 If the hemodynamic equator is on the donor side of the branching vessel, this system will serve as a functional RD. However, if the hemodynamic equator is on the recipient side of the branching vessel, the AA communication will serve as a functional DR. 

This relationship can only be ascertained in utero (Figure 5.9). Because the oxygenation content of the arterial systems of the donor vs recipient fetuses often varies, the color of the arterial blood from each twin may be discordant. This allows for fetoscopic identification of the hemodynamic equator. We have noted during endoscopic fetal surgery that the hemodynamic equator is not static: rather, it moves along the AA anastomosis. We have termed this phenomenon ‘flashing’.24 The reason for the movement of this collision front may have to do with the blood pressure that is mounted from the arterial systems of each fetus. Thus, it is possible that an AA that was once a functional DR may become a functional RD if the arterial blood pressure of the donor decreases and/or the recipient increases. Because hemodynamics may dictate directionality, assignment of type of AA anastomosis (functional DR vs functional RD) may only be possible in utero. 

Monochorionic placentas may be classified as it pertains to TTTS via the type of vascular anastomoses identified.25 Placenta type A is defined as having no anastomoses, type B as having AV anastomoses only, type C as having superficial anastomoses only, and type D as having AV and superficial anastomoses. Our group analyzed 131 monochorionic–diamniotic twin placentas using this classification during a 4-year span; 105 placentas were from patients previously treated for TTTS by laser and 26 were monochorionic twins, with no TTTS, delivered at our institution. Forty-five cases were excluded because of placental fragmentation or fixation. Of the 105 monochorionic placentas with TTTS, 0 were type A, 85 (81%) were type B, 1 (1%) was type C, and 19 (18%) were type D. Of the 26 non-TTTS monochorionic placentas, 4 (15%) were type A, 0 were type B, 17 (65%) were type C, and 5 (19%) were type D. This study showed an association between the development of TTTS and type of monochorionic placenta. TTTS did not develop in type A (no anastomoses) and was unlikely to develop in type C (superficial only), whereas the syndrome occurred in all cases of type B (AV only) and most cases of type D (AV + superficial) placentas. This study suggests that AV communications play a central role in the development of TTTS. In that AV communications appear to be an important factor in TTTS, what then is the role for superficial anastomoses? Some groups have reported that AA anastomoses are less common in TTTS and may be associated with improved perinatal outcomes.26,27 However, we caution against the notion that AA communications are always protective. In the study by Bermudez et al,26 the severity of disease was unrelated to the type of anastomosis. We have found that an AA anastomosis may or may not equilibrate the exchange of blood, depending on the nature of the vascular anatomy and hemodynamics. In fact, severe TTTS with only superficial anastomoses has been reported by our group.28 A factor that must be taken into account is whether the role of the AA in utero serves as a functional DR, RD, or both. Also, it must be remembered that the superficial vessel remains a conduit through which acute transfusion may occur in the face of the fetal demise of one twin. In this setting, demise of one twin may result in demise or serious neurological harm of the co-twin from back bleeding. VV anastomoses were shown to be associated with decreased perinatal survival in one study.26 Thus, superficial anastomoses do play an important role in TTTS, and should be targeted for ablation at the time of selective laser photocoagulation of communicating vessels. 

The number of vascular anastomoses and the risk of TTTS have also been studied. Bajoria et al27 initially demonstrated that the likelihood of TTTS was greater if fewer anastomoses were present. However, a co-author of that paper subsequently showed no relationship with TTTS and number of vascular communications.26 The study by Bermudez et al showed that the number of anastomoses was not different in monochorionic–diamniotic placentas complicated by TTTS vs controls.25 Although rare, the ‘circular vasculature’, a unique vascular pattern that has important clinical manifestations, should be addressed. A circular vascular pattern is one in which all the major placental vessels have anastomotic communications. Thus, each individual fetus has a paucity of its own designated placental territory. Rather, most of the blood volume is being exchanged through the anastomoses from one fetus to the other. If selective laser photocoagulation of communicating vessels is performed in such a case, there may be a high likelihood of a double fetal demise. Depending on the clinical manifestation and the severity of the TTTS, one may elect to forego laser surgery for amnioreductions. There are several limitations of the current studies that try to address the pathophysiology of TTTS in regards to the placental vascular anatomy. Most of these studies are conducted after delivery. As mentioned above, vascular changes may occur during the course of the pregnancy. Superficial anastomoses may not be interpretable in regards to directionality and this approach lends itself to a more qualitative assessment. A quantitative assessment of flow through the vascular communications can only be done in utero. 

What does the vascular caliber, the differential of the twins’ blood pressures, blood viscosity, or other changes in intrauterine fetal hemodynamics have to do with the pathophysiology of TTTS? Our group has reported a pilot study that attempted to measure blood flow through all vascular communications in utero.29 Recently, Lopriore et al developed a novel method to measure blood flow. They studied a unique case of TTTS syndrome treated with fetoscopic laser surgery. The ex-recipient subsequently became severely anemic and was treated with an intrauterine blood transfusion at 29 weeks’ gestation. 

After birth, a placental injection study identified residual unidirectional AV anastomoses from the ex-recipient to the ex-donor without AV anastomoses in the opposite direction. Prospective measurements of decreasing hemoglobin levels between the intrauterine transfusion and birth allowed calculation of the net blood flow through the AV anastomoses. In this case the anastomotic blood flow at 29 weeks’ gestation was 27.9 ml/24 h.30 While the net imbalance of blood flow between the fetuses is accepted as a central factor for the etiology of TTTS, the vascular communications may also serve as a conduit for the transfusion of other factors from one fetus to the other. Several studies have documented imbalances in hormone and protein levels, including atrial natriuretic peptide, renin, and antidiuretic hormone concentrations. 31–35 What is the role of the discordance in these and other factors in the pathophysiology and/or propagation of TTTS? Further refinement of in-utero techniques to measure fetal hemodynamics and proteins with correlation to placental anatomy may shed further light on this syndrome.